In 1991, the genetic causes of Charcot-Marie-Tooth disease (CMT) were completely unknown. By a decade later, MDA-funded scientists had helped identify 10 CMT-linked genes and found evidence for several others. (There are now thought to be more than 30 genes in which flaws can cause CMT.) This accomplishment has led to genetic testing for many types of CMT, which has greatly improved diagnosis.

Of equal importance, the ongoing hunt for CMT genes has given insights into treatments that might be used to stop or reverse the disorder.

As the CMT gene hunt continues, MDA-funded scientists are investigating how and why specific genetic mutations lead to different types of CMT. These insights are expected to lead to improved ability to predict the course of CMT in specific individuals and ultimately to treatments.

The current projects being pursued by MDA-supported CMT researchers include:

• a study of calcium handling in peripheral nerve fibers;
• a study of the effects of CMT-causing gene mutations in zebrafish;
• new strategies to protect nerve fibers in mice with a disease closely resembling type 1 CMT;
• an exploration of the possible role of proteins called aminoacyl-tRNA synthetases in peripheral nerve diseases;
• an exploration of the molecular players and potential targets for therapy in a type of CMT;
• a study of how a loss of function in a protein called fig4 leads to type 4 CMT;
• an exploration of the possibility that modulators of heat shock protein 90 may be therapeutic in CMT;
• identification of signaling pathways that influence nerve-fiber health and injury in CMT; and
• a project to understand the biochemical basis of type 2A CMT by understanding the functions of the protein known as mitofusin 2.

In addition to these specific projects, MDA is supporting the CMT North American Database, a secure repository of information about CMT provided by patients and families. MDA also is supporting the North American CMT Network, an extension to the database designed to provide an infrastructure for CMT research.

Clinical trials in CMT also are under way.